BIOTECHNOLOGY
The Crystal 16 is a
proven tool for co- crystal screening
Co-crystals can also be used if the solubility of a compound is too high and is absorbed too quickly in the body, modulating solubility for a sustained, slower release. One example of where this has been used is Ribavirin, an antiviral medication used to treat RSV infection and hepatitis C with barbituric acid.
IMPROVING TASTE Taste has been shown to be an important factor in the acceptability and willingness of a patient to take oral drug products, especially in children, adolescents and the elderly. Co-crystals can be formed with sweeteners and taste maskers as co-formers, which leads to an improvement in the taste of a drug. Tis can be relatively straightforward, as many sweeteners and taste maskers are already FDA approved for application in food.
Dr Thomas Kendall explores the advantages of co-crystallisation in drug development
CTHE BENEFITS OF O
ver the past decade, co- crystallisation has become an attractive alternative to improve the physiochemical properties of
drugs without affecting their pharmacology. As a result of the pharmaceutical benefits co-crystals exhibit, industrial interest is on the rise.
When developing a drug product, solid formulations such as tablets and capsules are often selected because of the benefits offered to patients. Tese benefits include high patient adherence, low variability between dosages and ease of taking the drug. However, solid formulations often have poor solubility, which can affect the absorption rate in the body. Tere are several possible solid forms that can be investigated as part of the drug development process, each offering different physicochemical properties. A common strategy to increase the solubility of an ionisable drug molecule is salt formation. However, this approach is not suitable for non-ionisable materials, meaning scientists
38
www.scientistlive.com O-CRYSTALS
may look at alternative methods for solid state optimisation.
CO-CRYSTALS FOR SOLUBILITY An alternative strategy for improving solid state properties is co-crystallisation. Te FDA defines co-crystals as “crystalline materials composed of two or more different molecules, typically API and co-formers, in the same crystal lattice”. Unlike salts, co-crystals do not rely on ionic interactions and can therefore be used for non-ionisable drugs.
An example of a drug that incorporates
co-crystals is Abilify, otherwise known as Aripiprazole, an antipsychotic used in the treatment of schizophrenia. Te drug exhibits poor aqueous solubility because of its 12 known anhydrous polymorphs. To improve the solubility and thermal stability of the drug, scientists used a co- crystal with fumaric acid. Tis ensured the drug would dissolve at the correct critical time.
Teophylline, for example, is a drug used in therapy for respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Scientists formed a co- crystal with saccharin, an artificial sweetener, which was found to improve the overall taste of the drug and mask bitterness.
THE CO-CRYSTAL SCREENING PROCESS For scientists looking to use co-crystals to optimise their API during drug development, co-crystal screening is needed to identify candidates for characterisation. Co-crystal screening can be achieved using a number of techniques, including liquid assisted grinding or decreasing the temperature and driving supersaturation. Certain co-crystals will only be formed using certain techniques so it is important to use a wide range of screening methods. To avoid missing co-crystals, scientists can employ a systematic approach, which will also aid further development in the scale-up phase. One popular tool for co-crystal screening
is the Crystal16, which can be used to design an extensive co-crystal screening program by measuring the clear points of a series of co-formers and the API using 16 parallel reactors. By measuring the saturation temperatures of the mixtures, the possibility for co-crystallisation can be easily assessed.
Dr Thomas Kendall is application specialist at Technobis Crystallization Systems.
www.crystallizationsystems.com
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60
